Numerous studies have shown that glucocorticoids inhibit reproductive function; however, only limited attention has been given to the site and/or mechanism of this action. The overall objective of the proposed investigation is to obtain new information concerning the basic mechanisms regulating gonadotropin secretion by the anterior pituitary gland. Both in vivo and in vitro experimental approaches will be utilized to study the inhibition of luteinizing hormone (LH) by steroids possessing glucocorticoid activity. The specific objecties are: 1) to evaluate the interactions of glucocorticoids and LH-releasing hormone (LRH) on the synthesis and release of LH from the anterior pituitary, and 2) to determine whether interactions exist between glucocortoids and gonadal steroids on the pituitary response to LRH. In the in vivo experiments, comparisons of pituitary responsiveness to LRH will be made to determine whether: 1) the inhibitory action of glucocorticoids on LH release is independent of estrogen action, or 2) the glucocorticoids attentuate the LH response by antagonizing estrogen action. The in vitro studies will be made using dissociated pituitary cell suspensions. The response to LRH as influenced by glucocorticoids and gonadal steroids will be determined. The primary purpose of these studies is to determine whether the glucocorticoids have an inhibitory action in vitro (i.e., a pituitary site of action). If so, the in vitro model would be utilized for experiments to study the biological mechanism of this inhibition. These studies would aid in our understanding of pituitary hormone secretion as regulated by interactions of LRH and steroid hormones. In addition, the experimental approach would be useful for studying the effects of steroids on the regulation of other anterior pituitary hormones. A better knowledge of some of the basic physiological and pharmacological actions of glucocorticoids and other steroids would provide a better rationale for their use in health and disease.